The first accurate structural characterization of the axial fragment in cobalamins, containing axial S ligand, is described and discussed. The preparations and the crystal structure determinations of two cobalamins, (SO(3)Cbl)(NH4). nH(2)O (1) and [(NH2)(2)CSCbl]Cl . nH(2)O (2), based on synchrotron data collected at 100 K, are reported. The Co-S distances in 1 (2.231 (1) Angstrom) and 2 (2.216(7) Angstrom) are very close, whereas the trans Co-NB3 distance of 2.134(7) Angstrom in 1 is significantly longer than that of 2.01(1) Angstrom in 2. This suggests that sulfite exerts a strong trans influence, close to that of a methyl group, whereas thiourea has a fairly weak trans influence, close to that of azide. An evaluation of the Co-NB3 and Go-SR distances, not yet experimentally determined, is given and allows us to suggest that the SR trans influence is greater than that of thiourea but significantly smaller than that of sulfite. These findings support the previous suggestion, based on structural and spectroscopic results for cobaloximes, that the thiolate ligation by homocysteine in MeCbl is unlikely to be an important step in the processes involving methionine synthase. Some features of the crystal chemistry, such as the crystal packing and the H-bond scheme among the crystallization water molecules, in 1 and 2, are also discussed in relation to those of other cobalamins.